Sh. Gerber et al., The top loops of the C-2 domains from synaptotagmin and phospholipase A(2)control functional specificity, J BIOL CHEM, 276(34), 2001, pp. 32288-32292
The phospholipid-binding specificities of C-2 domains, widely distributed C
a2+-binding modules, differ greatly despite similar three-dimensional struc
tures. To understand the molecular basis for this specificity, we have exam
ined the synaptotagmin 1 C(2)A domain, which interacts in a primarily elect
rostatic, Ca2+-dependent reaction with negatively charged phospholipids, an
d the cytosolic phospholipase A(2) (cPLA(2)) C-2 domain, which interacts by
a primarily hydrophobic Ca2+-dependent mechanism with neutral phospholipid
s. We show that grafting the short Ca2+-binding loops from the tip of the c
PLA(2) C-2 domain onto the top of the synaptotagmin I C(2)A domain confers
onto the synaptotagmin I C(2)A domain the phospholipid binding specificity
of the cPLA(2) C-2 domain, indicating that the functional specificity of C-
2 domains is determined by their short top loops.